Article
Journal of Medicinal Chemistry, 2010, Vol. 53, No. 19 7089
compound in 14% yield. 1H NMR (500 MHz, CD3OD) δ 8.28
(d, J = 8.2, 1H), 7.63 (s, 1H), 7.57 (d, J = 16.3, 1H), 7.52 (d, J =
8.3, 1H), 7.39 (dd, J = 7.8, 6.3, 3H), 7.01 (dd, J = 16.3, 2.0, 1H),
6.81-6.77 (m, 2H), 2.65 (s, 3H). 13C NMR (126 MHz, CD3OD)
δ 177.22, 156.97, 148.73, 138.68, 132.28, 131.54, 130.47, 127.33,
125.29, 124.45, 123.62, 118.60, 117.54, 117.11, 115.27, 18.16.
HRMS (ESI) calcd for C18H15NO2 [M þ H]þ: 278.117 56.
Found: 278.117 56.
145.18, 136.03, 131.52 (d, J = 9 Hz), 128.99, 128.94, 128.61,
124.76, 120.34 (d, J = 25.25), 113.44, 105.86 (d, J = 23.23 Hz),
26.58. HRMS (ESI) calcd for C17H13NBrFO [M þ H]þ:
346.023 73. Found: 346.024 79.
3-(Hex-1-ynyl)-6-methoxy-2-methylquinolin-4(1H)-one (23b).
Compound 23b was prepared using general method E. Yield:
32%. 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 9.2, 1H), 7.45
(d, J = 2.8, 1H), 7.25 (dd, J = 9.2, 2.8, 1H), 6.53 (s, 1H), 3.98 (s,
3H), 2.89 (t, J = 7.5, 2H), 2.80 (s, 4H), 1.82-1.77 (m, 2H), 1.48
(m, 2H), 0.99 (t, J = 7.4, 3H). 13C NMR (126 MHz, CDCl3) δ
159.79, 157.65, 154.44, 150.98, 141.11, 130.64, 121.57, 119.84,
116.93, 101.40, 101.39, 98.41, 55.89, 30.22, 28.42, 22.77, 22.56,
14.07. HRMS (ESI) calcd for C17H19NO2 [M þ H]þ: 270.148 86.
Found: 270.149 72.
3-Bromo-6-methoxy-2-methylquinolin-4(1H)-one (18). Com-
pound 18 was prepared following general procedure B. Yield:
77%, mp = 262- 264 °C. 1H NMR (400 MHz, DMSO) δ 12.11
(s, 1H), 7.49 (dd, J = 13.3, 5.9 Hz, 2H), 7.31 (dd, J = 9.0, 2.9 Hz,
1H), 3.83 (s, 3H), 2.54 (s, 3H). 13C NMR (101 MHz, DMSO) δ
170.32, 155.74, 147.37, 133.23, 123.78, 122.26, 119.62, 105.11,
104.46, 55.36, 21.27. HRMS (ESI) calcd for C11H 10BrNO2
[M þ H]þ: 267.996 77. Found: 267.997 89.
3-(Hex-1-ynyl)-2-methylquinolin-4(1H)-one (24b). Compound
24b was prepared using general method E. Yield: 15%. 1H NMR
(400 MHz, CDCl3) δ 8.15 (d, J = 8.0, 1H), 8.07 (d, J = 8.1, 1H),
7.57 (t, J = 7.3, 1H), 7.49 (t, J = 7.4, 1H), 6.48 (s, 1H), 2.85-2.78
(m, 5H), 1.79-1.72 (m, 2H), 1.43 (dd, J = 14.7, 7.3, 2H), 0.95 (t,
J = 7.3, 3H). 13C NMR (101 MHz, CDCl3) δ 159.87, 154.72,
153.74, 145.16, 128.84, 127.82, 125.90, 121.36, 119.84, 116.41,
101.23, 30.11, 28.28, 22.88, 22.47, 13.98. HRMS (ESI) calcd for
C16H17NO [M þ H]þ: 240.138 29. Found: 240.139 28.
3-Bromo-2,6-dimethylquinolin-4(1H)-one (19). Compound 19
was prepared following general procedure B. Yield: 60%, mp =
266- 268 °C. 1H NMR (400 MHz, DMSO) δ 12.07 (s, 1H), 7.88
(s, 1H), 7.51-7.41 (m, 2H), 2.54 (s, 3H), 2.40 (s, 3H). 13C NMR
(101 MHz, DMSO) δ 170.74, 148.07, 136.68, 133.19, 132.93,
124.36, 122.69, 117.73, 105.66, 21.32, 20.70. HRMS (ESI) calcd
for C11H10BrNO [M þ H]þ: 252.001 85. Found: 252.001 14.
HRMS (ESI) calcd for C19H25NO [M þ H]þ: 284.200 89.
Found: 284.201 12.
6-Chloro-3-(hex-1-ynyl)-2-methylquinolin-4(1H)-one (25b). Com-
pound 25b was prepared using general method E. Yield: 25%. 1H
NMR (400 MHz, CDCl3) δ 8.12 (d, J = 2.3, 1H), 7.98 (d, J = 9.0,
1H), 7.51 (dd, J = 9.0, 2.3, 1H), 6.52 (s, 1H), 2.87 (d, J = 7.5, 2H),
2.79 (s, 3H), 1.80-1.75 (m, 2H), 1.48-1.43 (m, 2H), 0.98 (d, J =
7.3, 3H). 13C NMR (101 MHz, CDCl3) δ 160.51, 154.10, 153.70,
143.52, 131.65, 130.66, 128.50, 122.02, 119.00, 116.99, 101.36, 30.10,
28.32, 22.98, 22.47, 13.98. HRMS (ESI) calcd for C16H16ClNO
[M þ H]þ: 274.099 32. Found: 274.100 55.
3,6-Dibromo-2-methylquinolin-4(1H)-one (20). Compound 20
was prepared following general procedure B. Yield: 70%, mp =
295- 296 °C. 1H NMR (400 MHz, DMSO) δ 12.30 (s, 1H), 8.16
(d, J = 2.2 Hz, 1H), 7.81 (dd, J = 8.8, 2.2 Hz, 1H), 7.52 (d, J =
8.8 Hz, 1H), 2.55 (s, 3H). 13C NMR (101 MHz, DMSO) δ
169.73, 149.16, 137.42, 134.52, 127.23, 123.98, 120.46, 116.07,
106.16, 21.43. HRMS (ESI) calcd for C10H7Br2NO [M þ H]þ:
315.896 72. Found: 315.897 22.
3-Bromo-6-chloro-2-methylquinolin-4(1H)-one (21). Compound
21 was prepared following general procedure B. Yield: 66%, mp =
288- 290 °C. 1H NMR (400 MHz, DMSO) δ 12.31 (s, 1H), 8.01
(d, J = 2.0 Hz, 1H), 7.70 (dd, J = 8.8, 2.2 Hz, 1H), 7.58 (d, J = 8.8
Hz, 1H), 2.56 (s, 3H). 13C NMR (101 MHz, DMSO) δ 169.84,
149.10, 137.15, 131.91, 128.11, 124.05, 123.57, 120.30, 106.12,
21.40. HRMS (ESI) calcd for C10H7BrClNO [M þ H]þ:
271.947 23. Found: 271.947 88.
6-Fluoro-3-(hex-1-ynyl)-2-methylquinolin-4(1H)-one (26b).Com-
pound 26b was prepared using general method E. Yield: 31%. 1H
NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 9.2, 5.2, 1H), 7.78 (dd,
J = 8.8, 2.8, 1H), 7.40-7.33 (m, 1H), 6.56 (s, 1H), 2.89 (t, J = 7.6,
2H), 2.82 (s, 3H), 1.84-1.77 (m, 2H), 1.50-1.45 (m, 2H), 0.99 (t,
J = 7.4, 3H). 13C NMR (101 MHz, CDCl3) δ 160.44, 160.38 (d,
J = 247.5), 152.98, 142.12, 131.38 (d, J = 9.09), 121.83, 117.41 (d,
J = 41), 116.86, 116.67, 104.88 (d, J = 24.24), 101.34, 30.09, 28.30,
22.77, 22.47, 13.97. HRMS (ESI) calcd for C16H16FNO [M þ H]þ:
258.128 87. Found: 258.129 03.
3-Bromo-6-fluoro-2-methylquinolin-4(1H)-one (22). Compound
22 was prepared following general procedure B. Yield: 67%, mp =
282- 285 °C. 1H NMR (400 MHz, DMSO) δ 12.29 (s, 1H), 7.73
(dd, J = 9.3, 2.4 Hz, 1H), 7.60 (qd, J = 9.1, 3.8 Hz, 2H), 2.56 (s,
3H). 13C NMR (101 MHz, DMSO) δ 170.18, 159.57, 157.16,
148.72, 135.29, 123.69, 120.50, 109.28, 105.40, 21.35. HRMS (ESI)
calcd for C10H7BrFNO [M þ H]þ: 255.976 78. Found: 255.977 63.
4-(Benzyloxy)-3-bromo-6-methoxy-2-methylquinoline (23a).
Compound 23a was prepared using general procedure C. Yield:
73%. 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 9.2, 1H), 7.55
(d, J = 6.3, 2H), 7.41 (t, J = 7.5, 3H), 7.30 (dd, J = 9.2, 2.8, 1H),
3-Benzyl-6-methoxy-2-methylquinolin-4(1H)-one (27). Com-
pound 27 was prepared following modified general procedure
A using CaSO4. Yield: 65%, mp = 294- 295 °C. 1H NMR (400
MHz, DMSO) δ 11.50 (s, 1H), 7.52 (d, J = 2.4 Hz, 1H), 7.46 (d,
1H), 7.27-7.06 (m, 6H), 3.91 (s, 2H), 3.82 (s, 3H), 2.32 (s, 3H).
13C NMR (101 MHz, DMSO) δ 174.94, 155.10, 146.08, 141.46,
133.89, 128.06, 128.03, 125.40, 124.50, 121.63, 119.34, 117.23,
104.45, 55.23, 30.04, 17.75. HRMS (ESI) calcd for C18H17NO2
[M þ H]þ: 280.133 21. Found: 280.132 37.
3-Benzyl-6-chloro-2-methylquinolin-4(1H)-one (28). Compound
28 was prepared following general procedure A. Yield: 77%, mp =
328- 329 °C. 1H NMR (400 MHz, DMSO) δ 11.69 (s, 1H), 8.03
(d, J = 2.3 Hz, 1H), 7.62 (dd, J = 8.8, 2.4 Hz, 1H), 7.53 (d, J = 8.8
Hz, 1H), 7.24-7.08 (m, 5H), 3.89 (s, 2H), 2.34 (s, 3H). 13C NMR
(101 MHz, DMSO) δ 174.45, 147.61, 140.99, 137.75, 131.22,
128.11, 127.98, 127.12, 125.51, 124.50, 124.12, 120.07, 118.58,
29.91, 17.89. HRMS (ESI) calcd for C17H14ClNO [M þ H]þ:
284.083 67. Found: 284.083 30.
7.13 (d, J = 2.8, 1H), 5.19 (s, 2H), 3.76 (s, 3H), 2.85 (s, 3H). 13
C
NMR (101 MHz, CDCl3) δ 158.72, 157.92, 156.47, 144.20,
136.60, 130.37, 128.93, 128.85, 128.68, 124.80, 122.82, 112.96,
99.96, 55.62, 26.37. HRMS (ESI) calcd for C18H16BrNO2 [M þ
H]þ: 358.043 72. Found: 358.045 07.
4-(Benzyloxy)-3-bromo-6-chloro-2-methylquinoline (25a). Com-
pound 25a was prepared using general method C. Yield: 74%. 1H
NMR (400 MHz, CDCl3) δ 7.92 (d, J = 9.3, 2H), 7.60 (dd, J =
8.9, 2.3, 1H), 7.56 (d, J=6.8, 2H), 7.46-7.39 (m, 3H), 5.20 (s, 2H),
2.88 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.87, 158.74,
146.40, 135.96, 132.54, 131.11, 130.58, 129.02, 128.93, 128.62,
124.63, 121.16, 113.43, 26.72. HRMS (ESI) calcd for
C17H13BrClNO [M þ H]þ: 361.994 18. Found: 361.994 14.
4-(Benzyloxy)-3-bromo-6-fluoro-2-methylquinoline (26a). Com-
pound 26a was prepared using general procedure C. Yield: 43%.
1H NMR (400 MHz, CDCl3) δ 8.00 (dd, J = 9.2, 5.2, 1H), 7.57 (d,
J = 6.5, 3H), 7.47-7.40 (m, 4H), 5.20 (s, 2H), 2.88 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ160.71 (d, J= 247 Hz), 159.04, 158.77,
6-Methoxy-2-methyl-3-phenylquinolin-4(1H)-one (29). Com-
pound 29 was prepared following general procedure A. Yield: 95%,
mp = 362- 362 °C. 1H NMR (400 MHz, DMSO) δ 11.62 (s, 1H),
7.50 (d, J = 8.9 Hz, 2H), 7.38 (t, J = 7.4 Hz, 2H), 7.32-7.21 (m,
4H), 3.82 (s, 3H), 2.20 (s, 3H). 13C NMR (101 MHz, DMSO) δ
174.11, 155.20, 145.54, 136.50, 134.01, 131.02, 127.71, 126.33,
125.35, 121.77, 119.91, 119.35, 104.69, 55.28, 18.82. HRMS (ESI)
calcd for C17H15NO2 [M þ H]þ: 266.117 56. Found: 266.117 18.
6-Chloro-2-methyl-3-phenylquinolin-4(1H)-one (30). Compound
30 was prepared following modified general procedure A using